Our goal is to commercialize a high-performance low-cost proton radiography system based on well-established fast scintillator technology. This system will produce images of patients in terms of proton stopping power, by tracking individual protons before and after the patient and measuring the proton residual range after traversing the patient. The design of our system is based on requirements that the final clinical detector be simple, lightweight, and easily scaled to large field sizes, operate at high speed to avoid bottlenecks in patient throughput, and expose the patient to the minimum possible dose for a given resolution. Radiation therapy is needed for more than 50% of the 1.6 million Americans who are annually diagnosed with cancer. A conservative estimate from the Mayo Clinic is that 137,000 new cancer patients each year in the United States could benefit from proton radiation therapy, well above current capacity. Proton radiation therapy can potentially spare large amounts of normal tissue from low to intermediate radiation dose and avoid organs at risk. This reduces late effects and improves quality of life, and is especially important for patients with high cure rates and long survival times. Proton radiography would be the most direct method of image guidance for proton therapy. There is a clear need to enable more complex treatments delivering a high dose to the tumor with reduced uncertainty margins [2,3]. There is also a clear need to increase patient throughput and improve the cost-effectiveness of proton therapy relative to conventional radiation therapy [6]. The use of a proton beam for both imaging and treatment streamlines patient setup and quality assurance procedures, reduces alignment uncertainties, and reduces proton range uncertainties. Our academic partner previously participated in the clinical implementation of an analogous strategy applying megavoltage CT to image guidance for adaptive helical tomotherapy [12]. In Phase 1, we propose to establish feasibility for both our residual range detector and our tracking detector. Our strategy is to buil prototype detectors with all the features needed to check high-speed operation, resolution, efficiency, and calibration strategies, and to analyze large data sets and develop detailed simulations for a thorough understanding for our system. Our specific objectives are: 1) Construct a prototype high-speed proton residual range detector. 2) Analyze range detector test beam and simulation data. 3) Construct and test a high-speed proton tracking detector prototype. In Phase 2, the combination of high performance, simple monolithic construction and reduced electronics channel count will enable us to propose construction of a full low-cost system and to start testing strategies to optimize treatments and improve patient throughput.